Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparame...Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparametric ultrasound(US)techniques to provide more accurate,objective,and non-invasive evaluations of liver fibrosis and steatosis.Analyzing large datasets from US images,AI enhances diagnostic precision,enabling better quantification of liver stiffness and fat content,which are essential for diagnosing and staging liver fibrosis and steatosis.Combining advanced US modalities,such as elastography and doppler imaging with AI,has demonstrated improved sensitivity in identifying different stages of liver disease and distinguishing various degrees of steatotic liver.These advancements also contribute to greater reproducibility and reduced operator dependency,addressing some of the limitations of traditional methods.The clinical implications of AI in liver disease are vast,ranging from early detection to predicting disease progression and evaluating treatment response.Despite these promising developments,challenges such as the need for large-scale datasets,algorithm transparency,and clinical validation remain.The aim of this review is to explore the current applications and future potential of AI in liver fibrosis and steatosis assessment using multiparametric US,highlighting the technological advances and clinical relevance of this emerging field.展开更多
The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble dif...The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.展开更多
The optimal development,function,and maintenance of the central nervous system(CNS)are determined by the dynamic and continuous crosstalk between its components.Neurons and glial cells,the cellular constituents of the...The optimal development,function,and maintenance of the central nervous system(CNS)are determined by the dynamic and continuous crosstalk between its components.Neurons and glial cells,the cellular constituents of the CNS,orchestrate a wide range of essential activities(Allen and Lyons,2018).Notably,glial cells,which outnumber neurons,constitute the major population within the CNS.This population comprises astrocytes,microglia,oligodendrocytes,and ependymal cells,each fulfilling specialized functions that contribute to neural homeostasis and overall CNS integrity.Astrocytes are pivotal in preserving structural and functional integrity through the regulation of synaptic function,the clearance of neurotransmitters,and ion balance.Moreover,they provide metabolic support to neurons.展开更多
Background:Double blind-ending ureter(DBU)is an extremely rare congenital anomaly involving a duplicated ureter with no connection to the renal pelvis or bladder,making diagnosis difficult.Case Description:A 10-year-o...Background:Double blind-ending ureter(DBU)is an extremely rare congenital anomaly involving a duplicated ureter with no connection to the renal pelvis or bladder,making diagnosis difficult.Case Description:A 10-year-old girl presented with recurrent abdominal pain and ultrasound evidence of left hydroureteronephrosis.Magnetic resonance imaging(MRI)and three-dimensional(3D)reconstruction revealed a 30 cm blind-ending ureter.Robotic-assisted excision(Da Vinci Xi)was performed safely,preserving adjacent structures.Histology confirmed a nonfunctional ureteral remnant.Conclusions:DBU is a rare duplication variant.Advanced imaging and robotic surgery are essential for accurate diagnosis and effective,minimally invasive treatment.展开更多
Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence ...Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.展开更多
Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It ...Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.展开更多
Background:The Da Vinci Single-Port Robotic System(Da Vinci-SP),introduced by Intuitive(CA,USA)in 2018 in the USA and in 2024 in Europe,integrates advanced features like a flexible camera and articulating instruments....Background:The Da Vinci Single-Port Robotic System(Da Vinci-SP),introduced by Intuitive(CA,USA)in 2018 in the USA and in 2024 in Europe,integrates advanced features like a flexible camera and articulating instruments.It has garnered significant interest in urology.Our report presents the first described European series of Radical Prostatectomies using the Da Vinci SP at the leading Italian center,Istituto Nazionale Tumori di Napoli,IRCCS“G.Pascale”Foundation,detailing the technical differences and challenges faced by experienced multiport robotic surgeons.Methods:Sixteen patients have been enrolled and underwent Single-Port(SP)Robot-Assisted Radical Prostatectomy(SP-RARP).Baseline characteristics of the patients were collected.We provided a step-by-step description of the surgical technique.Oncological outcomes have been evaluated and compared with magnetic resonance imaging(MRI)and biopsy results.Intraoperative,perioperative,and postoperative complications,surgical outcomes,functional outcomes,and technical issues of the new system were also documented.Results:All surgeries were successfully performed without the need for conversion.An extraperitoneal approach was used for all patients.Median Console time was 110 min.No complications were reported.The estimated median blood loss was 175 cc.Discharge from the hospital was on the first post-operative day for all patients.Bladder catheter removal was on day 7 without the need for cystography.Conclusions:We presented the first European case series of SP-RARP,reporting our experience and confirming the procedure’s feasibility for a highly experienced robotic surgeon.Experience with an extraperitoneal approach using the multiport(MP)platform,combined with well-conducted training for the SP system,may facilitate the transition to SP surgery.Further procedures and studies are needed to evaluate the oncological and functional outcomes.展开更多
BACKGROUND:Maxillofacial trauma represents a significant challenge in emergency medicine,requiring both diagnostic accuracy and prompt intervention while balancing immediate life-saving interventions with preservation...BACKGROUND:Maxillofacial trauma represents a significant challenge in emergency medicine,requiring both diagnostic accuracy and prompt intervention while balancing immediate life-saving interventions with preservation of function and aesthetics.The complex anatomy of this region,with its proximity to critical structures,demands a thorough understanding of assessment and management principles.This narrative review aims to provide evidence-based guidelines for emergency physicians managing maxillofacial trauma,with particular emphasis on early recognition of critical injuries,airway management strategies,and special population considerations.METHODS:A narrative review was conducted via a comprehensive literature search of the PubMed and Scopus databases,which focused on maxillofacial trauma management in emergency settings.Articles were selected based on relevance to clinical practice,methodological quality,and current management guidelines.The review synthesized evidence from multiple study types,including original research,systematic reviews,and clinical practice guidelines,to provide practical guidance for emergency physicians.RESULTS:Initial assessment following Advanced Trauma Life Support(ATLS)principles is crucial,with airway management being a primary concern due to the risk of dynamic obstruction.Critical time-sensitive emergencies include orbital compartment syndrome,trapdoor fractures(in pediatric patients),and facial nerve injuries.Computed tomography(CT)imaging remains the gold standard for diagnosis.Special considerations are required for pediatric patients,who present unique anatomical challenges and injury patterns,and for elderly patients,who often have complex medical comorbidities and increased complication risks.Management strategies range from conservative treatment to urgent surgical intervention,with decisions based on the injury pattern and associated complications.CONCLUSION:Emergency physicians must maintain a structured yet fl exible approach to maxillofacial trauma,focusing on early recognition of critical injuries,appropriate airway management,and timely specialist consultation.Understanding injury patterns and their potential complications allows for eff ective risk stratifi cation and treatment planning,ultimately improving patient outcomes.展开更多
Background:The topic of this review is the study of the gut microbiota(GM),and the use of probiotics,especially in humans,as a new frontier in the field of prevention and health in general.The beneficial effects and f...Background:The topic of this review is the study of the gut microbiota(GM),and the use of probiotics,especially in humans,as a new frontier in the field of prevention and health in general.The beneficial effects and functions performed by probiotics in the GM are increasingly at the centre of both scientific,medical,and pharmaceutical interest.It is now known that diet and probiotics can modify the GM,although in these situations there is a need for greater and more in-depth research regarding the methods and timing of treatment.However,the relationship between physical activity,GM,and probiotics is still largely unclear,as regards certain mechanisms between physical exercise and probiotics in humans.Discussion:In this study,we tried to demonstrate whether and how physical exercise was able to alter the composition of the microbiota and how probiotics can facilitate it.Therefore,alteration of the microbiota was considered in terms of both diversity and composition.Conclusions:The ones examined propose vastly different physical exercises,both in terms of timing and type of intervention itself,and the use of probiotics.展开更多
Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advanc...Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.展开更多
Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic ...Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.展开更多
Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central ne...Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.展开更多
The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As t...The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.展开更多
BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatm...BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatments.NLR has emer-ged as an indicator of systemic inflammation and physiological stress.NPR has emerged as a potential indicator of inflammation and thrombotic risk in the context of surgical and radiological procedures.AIM To analyze the correlation of NLR and NPR with the development of post-liver transplantation(LT)early complications after stratification for hepatocellular carcinoma diagnosis.METHODS Consecutive patients undergone LT between January 2019 and December 2023 were enrolled.Data regarding the concentration of hemoglobin and the differ-ential leukocyte count on postoperative days(POD)0,1,3,and 5 were collected.RESULTS The dataset included 161 consecutive patients undergone LT.Clavien-Dindo IV-V complications had a good correlation with NLR POD 1(P=0.05),NLR POD 3(P<0.001),NLR POD 7(P<0.001),NPR POD 3(P<0.001).In addition,the NPR ratio on POD 3 correlated with the onset of 30-day hemorrhage(P=0.009).Finally,30-day mortality had a significant association with the NLR POD 1(P=0.03)and with NLR POD 7(P=0.004),while NPR had a significant correlation with 30-day mortality in NPR POD 7(P=0.004).CONCLUSION The analysis of NLR and NPR are strictly correlated with Clavien-Dindo IV-V complications and 30-day post-LT death.展开更多
PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different patho...PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.展开更多
BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHOD...BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.展开更多
Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is importan...Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
This article aims to deepen the understanding of the role of Helicobacter pylori(H.pylori)infection in the development of cholelithiasis,initiated by the article by Yao et al,who investigated the potential link betwee...This article aims to deepen the understanding of the role of Helicobacter pylori(H.pylori)infection in the development of cholelithiasis,initiated by the article by Yao et al,who investigated the potential link between H.pylori infection and the development of cholelithiasis through a multicenter retrospective study on an Asian population of over 70000 participants.They also performed a compre-hensive analysis of previously published studies on H.pylori and cholelithiasis,finding a positive association therein[odds ratio(OR)=1.103,P=0.049].Patients positive for H.pylori also had lower levels of total and direct bilirubin,but higher levels of total cholesterol and low-density lipoprotein cholesterol compared to uninfected patients(P<0.05).Cohort studies have confirmed that H.pylori is a risk factor for cholelithiasis(P<0.0001),and aggregate analyses of case-control and cross-sectional studies have shown a positive association between H.pylori and cholelithiasis in Asia(OR=1.599,P=0.034),but not in Europe(OR=1.277,P=0.246).Moreover,H.pylori appears to be related to a higher ratio of choledocho-lithiasis/cholecystolithiasis(OR=3.321,P=0.033).The authors conclude that H.pylori infection is positively correlated with cholelithiasis,particularly with the choledocholithiasis phenotype,especially in Asia,and it is potentially related to bilirubin and cholesterol metabolism.展开更多
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
文摘Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparametric ultrasound(US)techniques to provide more accurate,objective,and non-invasive evaluations of liver fibrosis and steatosis.Analyzing large datasets from US images,AI enhances diagnostic precision,enabling better quantification of liver stiffness and fat content,which are essential for diagnosing and staging liver fibrosis and steatosis.Combining advanced US modalities,such as elastography and doppler imaging with AI,has demonstrated improved sensitivity in identifying different stages of liver disease and distinguishing various degrees of steatotic liver.These advancements also contribute to greater reproducibility and reduced operator dependency,addressing some of the limitations of traditional methods.The clinical implications of AI in liver disease are vast,ranging from early detection to predicting disease progression and evaluating treatment response.Despite these promising developments,challenges such as the need for large-scale datasets,algorithm transparency,and clinical validation remain.The aim of this review is to explore the current applications and future potential of AI in liver fibrosis and steatosis assessment using multiparametric US,highlighting the technological advances and clinical relevance of this emerging field.
基金supported by FATALSDrug Project [Progetti di Ricerca@CNR SAC.AD002.173.058] from National Research Council,Italy (to CV)。
文摘The NSC-34 cell line is a widely recognized motor neuron model and various neuronal differentiation protocols have been exploited. Under previously reported experimental conditions, only part of the cells resemble differentiated neurons;however, they do not exhibit extensive and time-prolonged neuritogenesis, and maintain their duplication capacity in culture. The aim of the present work was to facilitate long-term and more homogeneous neuronal differentiation in motor neuron–like NSC-34 cells. We found that the antimitotic drug cytosine arabinoside promoted robust and persistent neuronal differentiation in the entire cell population. Long and interconnecting neuronal processes with abundant growth cones were homogeneously induced and were durable for up to at least 6 weeks in culture. Moreover, cytosine arabinoside was permissive, dispensable, and mostly irreversible in priming NSC-34 cells for neurite initiation and regeneration after mechanical dislodgement. Finally, the expression of the cell proliferation antigen Ki67 was inhibited by cytosine arabinoside, whereas the expression levels of neuronal growth associated protein 43, vimentin, and motor neuron–specific p75, Islet2, homeobox 9 markers were upregulated, as confirmed by western blot and/or confocal immunofluorescence analysis. Overall, these findings support the use of NSC-34 cells as a motor neuron model for properly investigating neurodegenerative mechanisms and prospectively identifying neuroprotective strategies.
基金supported by Linea D.1.2023-24 UniversitàCattolica del S.Cuore(to MTV).
文摘The optimal development,function,and maintenance of the central nervous system(CNS)are determined by the dynamic and continuous crosstalk between its components.Neurons and glial cells,the cellular constituents of the CNS,orchestrate a wide range of essential activities(Allen and Lyons,2018).Notably,glial cells,which outnumber neurons,constitute the major population within the CNS.This population comprises astrocytes,microglia,oligodendrocytes,and ependymal cells,each fulfilling specialized functions that contribute to neural homeostasis and overall CNS integrity.Astrocytes are pivotal in preserving structural and functional integrity through the regulation of synaptic function,the clearance of neurotransmitters,and ion balance.Moreover,they provide metabolic support to neurons.
文摘Background:Double blind-ending ureter(DBU)is an extremely rare congenital anomaly involving a duplicated ureter with no connection to the renal pelvis or bladder,making diagnosis difficult.Case Description:A 10-year-old girl presented with recurrent abdominal pain and ultrasound evidence of left hydroureteronephrosis.Magnetic resonance imaging(MRI)and three-dimensional(3D)reconstruction revealed a 30 cm blind-ending ureter.Robotic-assisted excision(Da Vinci Xi)was performed safely,preserving adjacent structures.Histology confirmed a nonfunctional ureteral remnant.Conclusions:DBU is a rare duplication variant.Advanced imaging and robotic surgery are essential for accurate diagnosis and effective,minimally invasive treatment.
文摘Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.
基金supported by Italian Ministry of Health Ricerca Corrente [RC 2023] and RF-2016-02361294supported by#NEXTGENERATIONEU (NGEU)+3 种基金funded by the Ministry of University and Research (MUR)National Recovery and Resilience Plan (NRRP)project MNESYS (PE0000006)–A Multiscale integrated approach to the study of the nervous system in health and disease (DN. 1553 11.10.2022)(to FRG)partially supported by a grant from Fondazione Romeo ed Enrica Invernizzi (to FRG)。
文摘Multiple sclerosis(MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system(CNS) with a neurodegenerative component, characterized by demyelination and degeneration of nerve fibers. It affects mainly young adults(aged 20 to 45 years) and its causes are still unknown, but it is thought that external factors such as viruses and environmental factors trigger the disease in people with a genetic susceptibility.
文摘Background:The Da Vinci Single-Port Robotic System(Da Vinci-SP),introduced by Intuitive(CA,USA)in 2018 in the USA and in 2024 in Europe,integrates advanced features like a flexible camera and articulating instruments.It has garnered significant interest in urology.Our report presents the first described European series of Radical Prostatectomies using the Da Vinci SP at the leading Italian center,Istituto Nazionale Tumori di Napoli,IRCCS“G.Pascale”Foundation,detailing the technical differences and challenges faced by experienced multiport robotic surgeons.Methods:Sixteen patients have been enrolled and underwent Single-Port(SP)Robot-Assisted Radical Prostatectomy(SP-RARP).Baseline characteristics of the patients were collected.We provided a step-by-step description of the surgical technique.Oncological outcomes have been evaluated and compared with magnetic resonance imaging(MRI)and biopsy results.Intraoperative,perioperative,and postoperative complications,surgical outcomes,functional outcomes,and technical issues of the new system were also documented.Results:All surgeries were successfully performed without the need for conversion.An extraperitoneal approach was used for all patients.Median Console time was 110 min.No complications were reported.The estimated median blood loss was 175 cc.Discharge from the hospital was on the first post-operative day for all patients.Bladder catheter removal was on day 7 without the need for cystography.Conclusions:We presented the first European case series of SP-RARP,reporting our experience and confirming the procedure’s feasibility for a highly experienced robotic surgeon.Experience with an extraperitoneal approach using the multiport(MP)platform,combined with well-conducted training for the SP system,may facilitate the transition to SP surgery.Further procedures and studies are needed to evaluate the oncological and functional outcomes.
文摘BACKGROUND:Maxillofacial trauma represents a significant challenge in emergency medicine,requiring both diagnostic accuracy and prompt intervention while balancing immediate life-saving interventions with preservation of function and aesthetics.The complex anatomy of this region,with its proximity to critical structures,demands a thorough understanding of assessment and management principles.This narrative review aims to provide evidence-based guidelines for emergency physicians managing maxillofacial trauma,with particular emphasis on early recognition of critical injuries,airway management strategies,and special population considerations.METHODS:A narrative review was conducted via a comprehensive literature search of the PubMed and Scopus databases,which focused on maxillofacial trauma management in emergency settings.Articles were selected based on relevance to clinical practice,methodological quality,and current management guidelines.The review synthesized evidence from multiple study types,including original research,systematic reviews,and clinical practice guidelines,to provide practical guidance for emergency physicians.RESULTS:Initial assessment following Advanced Trauma Life Support(ATLS)principles is crucial,with airway management being a primary concern due to the risk of dynamic obstruction.Critical time-sensitive emergencies include orbital compartment syndrome,trapdoor fractures(in pediatric patients),and facial nerve injuries.Computed tomography(CT)imaging remains the gold standard for diagnosis.Special considerations are required for pediatric patients,who present unique anatomical challenges and injury patterns,and for elderly patients,who often have complex medical comorbidities and increased complication risks.Management strategies range from conservative treatment to urgent surgical intervention,with decisions based on the injury pattern and associated complications.CONCLUSION:Emergency physicians must maintain a structured yet fl exible approach to maxillofacial trauma,focusing on early recognition of critical injuries,appropriate airway management,and timely specialist consultation.Understanding injury patterns and their potential complications allows for eff ective risk stratifi cation and treatment planning,ultimately improving patient outcomes.
文摘Background:The topic of this review is the study of the gut microbiota(GM),and the use of probiotics,especially in humans,as a new frontier in the field of prevention and health in general.The beneficial effects and functions performed by probiotics in the GM are increasingly at the centre of both scientific,medical,and pharmaceutical interest.It is now known that diet and probiotics can modify the GM,although in these situations there is a need for greater and more in-depth research regarding the methods and timing of treatment.However,the relationship between physical activity,GM,and probiotics is still largely unclear,as regards certain mechanisms between physical exercise and probiotics in humans.Discussion:In this study,we tried to demonstrate whether and how physical exercise was able to alter the composition of the microbiota and how probiotics can facilitate it.Therefore,alteration of the microbiota was considered in terms of both diversity and composition.Conclusions:The ones examined propose vastly different physical exercises,both in terms of timing and type of intervention itself,and the use of probiotics.
文摘Overview:Surgical management of benign prostatic hyperplasia(BPH)has evolved significantly,incorporating various minimally invasive procedures aimed at reducing morbidity and optimizing patient outcomes.Despite advancements,transurethral approaches continue to pose risks such as urethral strictures and urinary incontinence due to mechanical and thermal stress.To address these limitations,the Suprapubic Transvesical Adenoma Resection of the Prostate(STARP)was developed,offering a direct suprapubic route that bypasses the urethra entirely.Recent studies have validated STAR-P as both feasible and safe,emphasizing advantages such as enhanced visualization of the urinary sphincter,minimized urethral trauma,effective hemostasis,and reduced operative stress.The procedure utilizes specially designed instrumentation,including a large-caliber bipolar resectoscope(42 Fr),allowing the efficient removal of substantial adenoma tissue in fewer resection passes compared to traditional methods.Objectives:This article provides a comprehensive,step-by-step description of the STAR-P technique.The primary objective is to detail patient selection criteria,preoperative assessments,procedural steps including mini-open suprapubic access,specialized instrumentation usage,resection techniques,and postoperative management protocols.Highlighting technical considerations and procedural innovations aims to inform urologists about the potential benefits of STAR-P,particularly in patients at higher risk for urethral complications or those with large prostate volumes.By documenting the procedural intricacies and outcomes clearly and thoroughly,we seek to encourage informed adoption of STAR-P as an alternative,effective surgical approach for managing benign prostatic hyperplasia,thus contributing to the evolving landscape ofminimally invasive urological surgery.
文摘Complex genetic relationships between neurodegenerative disorders and neuropsychiatric symptoms have been shown, suggesting shared pathogenic mechanisms and emphasizing the potential for developing common therapeutic targets. Apolipoprotein E(APOE) genotypes and their corresponding protein(Apo E) isoforms may influence the biophysical properties of the cell membrane lipid bilayer. However, the role of APOE in central nervous system pathophysiology extended beyond its lipid transport function. In the present review article, we analyzed the links existing between APOE genotypes and the neurobiology of neuropsychiatric symptoms in neurodegenerative and vascular diseases. APOE genotypes(APOE ε2, APOE ε3, and APOE ε4) were implicated in common mechanisms underlying a wide spectrum of neurodegenerative diseases, including sporadic Alzheimer's disease, synucleinopathies such as Parkinson's disease and Lewy body disease, stroke, and traumatic brain injury. These shared pathways often involved neuroinflammation, abnormal protein accumulation, or responses to acute detrimental events. Across these conditions, APOE variants are believed to contribute to the modulation of inflammatory responses, the regulation of amyloid and tau pathology, as well as the clearance of proteins such as α-synuclein. The bidirectional interactions among Apo E, amyloid and mitochondrial metabolism, immunomodulatory effects, neuronal repair, and remodeling underscored the complexity of Apo E's role in neuropsychiatric symptoms associated with these conditions since from early phases of cognitive impairment such as mild cognitive impairment and mild behavioral impairment. Besides Apo E-specific isoforms' link to increased neuropsychiatric symptoms in Alzheimer's disease(depression, psychosis, aberrant motor behaviors, and anxiety, not apathy), the APOE ε4 genotype was also considered a significant genetic risk factor for Lewy body disease and its worse cognitive outcomes. Conversely, the APOE ε2 variant has been observed not to exert a protective effect equally in all neurodegenerative diseases. Specifically, in Lewy body disease, this variant may delay disease onset, paralleling its protective role in Alzheimer's disease, although its role in frontotemporal dementia is uncertain. The APOE ε4 genotype has been associated with adverse cognitive outcomes across other various neurodegenerative conditions. In Parkinson's disease, the APOE ε4 allele significantly impacted cognitive performance, increasing the risk of developing dementia, even in cases of pure synucleinopathies with minimal co-pathology from Alzheimer's disease. Similarly, in traumatic brain injury, recovery rates varied, with APOE ε4 carriers demonstrating a greater risk of poor long-term cognitive outcomes and elevated levels of neuropsychiatric symptoms. Furthermore, APOE ε4 influenced the age of onset and severity of stroke, as well as the likelihood of developing stroke-associated dementia, potentially due to its role in compromising endothelial integrity and promoting blood–brain barrier dysfunction.
文摘Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
文摘The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.
文摘BACKGROUND The use of biomarkers,such as the neutrophil-to-lymphocyte ratio(NLR)and the neutrophil-to-platelet ratio(NPR),has shown promise in evaluating early outcomes after medical,interventional,and surgical treatments.NLR has emer-ged as an indicator of systemic inflammation and physiological stress.NPR has emerged as a potential indicator of inflammation and thrombotic risk in the context of surgical and radiological procedures.AIM To analyze the correlation of NLR and NPR with the development of post-liver transplantation(LT)early complications after stratification for hepatocellular carcinoma diagnosis.METHODS Consecutive patients undergone LT between January 2019 and December 2023 were enrolled.Data regarding the concentration of hemoglobin and the differ-ential leukocyte count on postoperative days(POD)0,1,3,and 5 were collected.RESULTS The dataset included 161 consecutive patients undergone LT.Clavien-Dindo IV-V complications had a good correlation with NLR POD 1(P=0.05),NLR POD 3(P<0.001),NLR POD 7(P<0.001),NPR POD 3(P<0.001).In addition,the NPR ratio on POD 3 correlated with the onset of 30-day hemorrhage(P=0.009).Finally,30-day mortality had a significant association with the NLR POD 1(P=0.03)and with NLR POD 7(P=0.004),while NPR had a significant correlation with 30-day mortality in NPR POD 7(P=0.004).CONCLUSION The analysis of NLR and NPR are strictly correlated with Clavien-Dindo IV-V complications and 30-day post-LT death.
基金supported by Telethon Italy award GGP15225(to RC and GM)Italian Ministry of Health award RF-2016-02362950(to RC and CZ)+1 种基金the CJD Foundation USA(to RC)the Associazione Italiana Encefalopatie da Prioni(AIEnP)(to RC).
文摘PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.
文摘BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.
文摘Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
文摘This article aims to deepen the understanding of the role of Helicobacter pylori(H.pylori)infection in the development of cholelithiasis,initiated by the article by Yao et al,who investigated the potential link between H.pylori infection and the development of cholelithiasis through a multicenter retrospective study on an Asian population of over 70000 participants.They also performed a compre-hensive analysis of previously published studies on H.pylori and cholelithiasis,finding a positive association therein[odds ratio(OR)=1.103,P=0.049].Patients positive for H.pylori also had lower levels of total and direct bilirubin,but higher levels of total cholesterol and low-density lipoprotein cholesterol compared to uninfected patients(P<0.05).Cohort studies have confirmed that H.pylori is a risk factor for cholelithiasis(P<0.0001),and aggregate analyses of case-control and cross-sectional studies have shown a positive association between H.pylori and cholelithiasis in Asia(OR=1.599,P=0.034),but not in Europe(OR=1.277,P=0.246).Moreover,H.pylori appears to be related to a higher ratio of choledocho-lithiasis/cholecystolithiasis(OR=3.321,P=0.033).The authors conclude that H.pylori infection is positively correlated with cholelithiasis,particularly with the choledocholithiasis phenotype,especially in Asia,and it is potentially related to bilirubin and cholesterol metabolism.
